AB0046 OMEGA-3 EPOXIDES AMELIORATE MURINE INFLAMMATORY ARTHRITIS
Authors: A. Yoshida, K. Murakami, H. Tsukamoto, Y. Nakayama, R. Saito, M. Shirakashi, H. Tsuji, R. Hiwa, K. Kitagori, S. Akizuki, R. Nakashima, H. Yoshifuji, H. Onizawa, A. Onishi, M. Tanaka, A. Morinobu
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Epoxy fatty acids (EpFA), cytochrome P450(CYP)-mediated metabolites of polyunsaturated fatty acids (PUFA), have anti-inflammatory effects<sup>[1]</sup>. However, EpFA is quickly converted to an inactive form by the soluble epoxide hydrolase(sEH). In recent years, the efficacy of sEH inhibitors (sEHi) has been reported in a variety of diseases<sup>[2-4]</sup>. However, compared to ω-6 epoxides, such as epoxyeicosatirienioic acids (EET) derived from arachidonic acid (AA), there are few reports on ω-3 epoxides, epoxyeicosapentaenoic acid (EEQ) from eicosapentaenoic acid (EPA) and epoxydocosapentaenoic acids (EDP) from docosapentaenoic acid (DHA)5), and their effects on arthritis are not well understood. <h3>Objectives</h3> To investigate and compare the effects of ω-6 and ω-3 epoxides on inflammatory arthritis. <h3>Methods</h3> Collagen induced arthritis (CIA) were treated with three different diets (ω-6 PUFA rich, ω-3 PUFA rich, and Control) and two types of drinking solution, one containing sEHi and the other containing only polyethylene glycol as solvent control (total 6 groups, 8 mice each). Arthritis and pathological scores were evaluated, and feces were collected before the onset of arthritis (day 25) for intergroup comparative analysis of bacterial flora. <h3>Results</h3> In all the dietary groups, there was a tendency for arthritis scores to decrease with sEHi administration, but the incidence of arthritis, arthritis scores, and pathological scores decreased dramatically in the group fed with the ω-3 rich diet and sEHi combination. The groups fed the ω-6 rich diet and Control diet showed almost similar results. In the ω-3 rich diet and sEHi combination group, showed an increase in a certain specific bacterial strain. <h3>Conclusion</h3> ω-3 epoxides were found to be more effective in reducing arthritis, and changes in intestinal bacteria may have influenced this pathological change. <h3>References</h3> [1]Shi, Z. et al. CYP450 Epoxygenase Metabolites, Epoxyeicosatrienoic Acids, as Novel Anti-Inflammatory Mediators. Molecules 2022,27,3873 [2]Sandra, C. et al. Discovery and In Vivo Proof of Concept of a Highly Potent Dual Inhibitor of Soluble Epoxide Hydrolase and Acetylcholinesterase for the Treatment of Alzheimer's Disease. J.Med.Chem,2022,65,4909-4925 [3]Merce, P.et al. Soluble Epoxide Hydrolase Inhibition to Face Neuroinflammation in Parkinson's Disease: A New Therapeutic Strategy.Biomolecules 2020, 10, 703; doi:10.3390/biom10050703 [4]Rebecca, L.et al. Protection from hypertension in mice by the Mediterranean diet is mediated by nitro fatty acid inhibition of soluble epoxide hydrolase. PNAS,2014,22,111,8167-8172 [5]Yang, Y. et al. Differential Effects of 17,18-EEQ and 19,20-EDP Combined with Soluble Epoxide Hydrolase Inhibitor t-TUCB on Diet-Induced Obesity in Mice. Int. J. Mol. Sci. 2021,22,8267 g. Characters from table content including title and footnotes. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.